Development of the pituitary gland relies on the proper spatial and temporal expression of extrinsic factors produced by the surrounding tissue and transcription factors intrinsic to the pituitary. These signals serve to control the specification and proliferation of the 5 hormone producing cell types of the anterior pituitary gland. A common disease that results from a defective pituitary deirelopment is combined pituitary hormone deficiency (CPHD). One gene known to be mutated in this disease is Prop1. Patients as well as mice with mutations in Propl present with decreased or negligible levels of the serum hormones thyrotropin, growth hormone, prolactin and gonadotropins. Decreased pituitary volume results from failure of the cells that produce these hormones to proliferate. To define the role of Propl in pituitary cell proliferation, the following studies will be performed: characterize the phenotype of pituitaries in which Propl is either absent or overexpressed persistently, and validate and characterize putative Propl target genes.